Targeted uptake of therapeutic nanoparticles (NPs) in a cell represents a powerful technology. Such NPs have the ability to encapsulate drugs and release them through surface or bulk erosion of the particles, diffusion of the drug, and/or swelling followed by diffusion of the drug. NPs offer enormous potential for surface engineering to introduce ligands such as peptides, antibodies, and nucleic acid aptamers, which can target delivery of the drug to cells of interest. Encapsulation of a drug within the interior of the particle may also protect the drug from the external environment, thus increasing the blood circulation time of the active dose before it reaches the target. Biodegradable particles have been developed as sustained release vehicles used in the administration of small molecule drugs as well as protein and peptide drugs and nucleic acids. The drugs are typically encapsulated in a matrix (e.g. polymer matrix) which is biodegradable and biocompatible. As the matrix is degraded and/or as the drug diffuses out of the particles, the drug is released into the body. Typically, polymers may be used to prepare these particles, for example, polyesters such as poly(lactide-co-glycolide) (PLGA), polyglycolic acid, poly-beta-hydroxybutyrate, polyacrylic acid ester, etc. In some cases, a particle may also protect a drug from degradation by the body prior to release at the targeted location. Furthermore, particles can be administered using a wide variety of administration routes.
Targeting controlled release polymer systems (e.g., targeted to a particular tissue or cell type or targeted to a specific diseased tissue but not normal tissue) is desirable in many situations because it reduces the amount of a drug present in tissues of the body that are not targeted. This can be particularly important when treating a condition such as cancer where it is desirable that a cytotoxic dose of the drug is delivered to cancer cells without killing the surrounding non-cancerous tissue. Effective drug targeting may reduce the undesirable and sometimes life threatening side effects common in anticancer therapy.
In some cases, encapsulation of certain drugs or drug precursors has been met with limited success. For example, it may be difficult to encapsulate a drug or drug precursor in a particle which is suitable for delivery to a patient due to the incompatibility of the drug or drug precursor with commonly used systems for drug delivery. For example, cisplatin, an FDA approved drug for cancer treatment, is generally insoluble in organic solvents and partial solubility in water and there have been limited successes in encapsulating the cisplatin drug in certain commonly used materials for delivery (e.g., PLGA).
Accordingly, improved systems and methods are needed for delivering drugs or drug precursors in particles.